Contact between SIV-infected sooty mangabeys and other primate species probably led to cross-species viral transmission resulting in epidemics of lymphoma in rhesus macaques, PML in stump-tailed macaques, and HIV-2-related AIDS in humans. We have previously documented that sooty mangabeys have high viral load and high viral diversity. This may facilitate cross-species transmission by increasing the infectiousness of mangabeys and by increasing the likelihood that a viral variant will be present which can replicate in a new host species. During this year, studies of viral diversity in sooty mangabeys were expanded to a cross-sectional study of 15 mangabeys and a longitudinal study of 5 mangabeys. The majority of viral genetic variation in mangabeys consisted of synonymous mutations arguing that SIV has achieved an equilibrium in its natural host. Also consistent with host-virus equilibrium, we found that the viral diversity pattern in mangabeys remained constant in 4 man gabeys studied over a 12 week period. In one mangabey, there was evidence for massive extinction of viral variants over a twelve week period but no further change in viral diversity over the ensuing six months. These preliminary data suggest that viral diversification in mangabeys occurs in bursts, similar to the sporadic evolution recently observed in bacterial cultures. These data are consistent with recently described theories of co-evolution and have implications for some aspects of phylogentic analysis. Evidence for mangabey co-evolution with SIV was sought through a study of the frequency of CD4 alleles in the mangabey colony at Yerkes. An assay was developed and validated to study mangabey CD4 haplotype in this study period. Analysis of DNA from 130 mangabeys indicated frequent occurrence of the two known CD4 alleles, but no evidence for a selective advantage for the heterozygous haplotype. The two CD4 alleles were cloned into eukaryotic expression vectors during this stu dy period and studies of SIV-CD4 interactions are planned. These studies may reveal novel determinants of viral diversification that may be involved in cross-species viral transmission and the emergence of new infectious diseases.